Prevalence of anti-SARS-CoV-2 Antibodies Among Cancer Patients and General Population in Dub-Saharan Africa

Ashley Clegg Author

08/03/2021 Added

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2021 Summer UCARE research on cross-reactivity contributing to partial protection against SARS-CoV-2 and COVID-19 disease pathogenesis.

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[00:00:00.630]Hi, my name is Ashley Clegg, and for my summer UCARE project,
[00:00:04.020]I researched in Dr. Charles Woods lab to study the prevalence of anti SARS-CoV-2
[00:00:08.010]antibodies among cancer patients and the general population in
[00:00:11.580]Sub-Saharan Africa
[00:00:12.690]and the US. At the beginning of the COVID-19 pandemic countries in Sub-Saharan
[00:00:17.340]Africa reported a mortality rate, much lower than other countries,
[00:00:20.430]such as the U S.
[00:00:21.750]This was surprising as the less developed medical infrastructure and high
[00:00:25.140]infectious disease burden in this region led experts to expect Africans to get
[00:00:29.100]hit harder by the pandemic.
[00:00:31.140]Despite a very low vaccination rate amidst the emergence of the pervasive Delta
[00:00:35.160]variant, Subsaharan Africa still fares better than expected.
[00:00:39.390]One theory to explain this is that the African population has been more exposed
[00:00:43.500]to other Coronaviruses prior to the pandemic.
[00:00:46.170]And this exposure resulted in a cross-reactive or cross protective immune
[00:00:50.040]response. In addition,
[00:00:52.110]it is expected that due to immunosuppression individuals with cancer will
[00:00:56.100]experience more severe
[00:00:57.720]disease pathogenesis and higher mortality than individuals without cancer.
[00:01:02.790]Next, I will expand on the structure of SARS-CoV-2
[00:01:05.400]and the concept of cross-reactivity COVID-19 is caused by severe acute
[00:01:10.140]respiratory syndrome, coronavirus two, which is an RNA virus,
[00:01:14.040]SARS-CoV-2 has four main structural proteins.
[00:01:18.450]Two of which are highly immunogenic,
[00:01:20.430]meaning they produce an immune response in the host.
[00:01:23.550]The first of these two proteins is the spike protein located on the surface of
[00:01:27.810]the virus.
[00:01:29.010]The spike protein allows the virus to attach to the host cell and enter it.
[00:01:33.450]It also contains the receptor binding domain,
[00:01:36.150]which is the target of neutralizing antibodies.
[00:01:38.970]The nucleocapsid protein resides inside the virus and assists with the
[00:01:42.540]efficiency of virus transcription and assembly.
[00:01:45.840]The nucleocapsid protein is expressed in plasma samples during the early stages
[00:01:49.830]of infection,
[00:01:51.060]the spike protein is associated with a higher neutralizing capacity indicating
[00:01:54.960]that patients with a positive spike protein response may have greater protection
[00:01:58.500]from severe illness due to COVID-19. In fact,
[00:02:01.560]all of the approved COVID-19 vaccines use the spike protein
[00:02:06.930]in this project, we tested the antibody response of patients,
[00:02:09.810]plasma samples with the hypothesis that those from sub Subsaharan Africa would
[00:02:14.130]demonstrate cross reactivity for SARS COV-2 to, to explain cross reactivity.
[00:02:19.200]The variable region of an antibody binds to certain proteins on.
[00:02:22.440]A pathogen called antigens.
[00:02:24.660]Typically an antibody recognizes and binds to an antigen specific to the
[00:02:28.500]pathogen. The antibody was made to fight. However,
[00:02:31.380]if the structure of a different antigen is similar enough,
[00:02:34.080]that antibody can also bind to that.
[00:02:35.820]Antigen. This phenomenon is called cross-reactivity cross-reactivity.
[00:02:40.380]May confer across protective immunity,
[00:02:42.450]especially essentially meaning that being exposed to a virus may provide some
[00:02:46.710]future protection against other viruses that are similar to it.
[00:02:51.540]The first objective of our research is to compare the prevalence of
[00:02:54.810]cross-reactive antibodies and plasma samples from Sub-Saharan Africa.
[00:02:58.530]And the S the second objective is first to determine if cancer patients are more
[00:03:03.010]susceptible to SARS cov, two infection, and second to compare cancer.
[00:03:07.000]And non-cancer sample is collected before and during the pandemic to see a
[00:03:10.880]preexisting cross-reactivity will help to reduce infection or severity of
[00:03:14.770]infection.
[00:03:18.160]The study cohort design is outlined in the tables on the slide around a hundred
[00:03:22.480]pre pandemic plasma samples.
[00:03:23.860]Each were analyzed from Tanzania Zambia and the U S for the cross-reactivity
[00:03:28.210]study with the cancer study samples collected prior to the pandemic from around
[00:03:32.620]400 cancer patients and 900 donors without cancer without cancer were analyzed.
[00:03:37.780]The HIV status was also recorded for considerations of co-morbidity a similar
[00:03:42.640]number of cancer and non cation cancer samples are being collected during the
[00:03:46.330]pandemic and will be compared to the pre pandemic cohort.
[00:03:51.730]Plasma samples were tested for antibody response using immunofluorescence assay
[00:03:55.690]or IFA against the spike and nuclear capsid proteins of the following Corona
[00:03:59.650]viruses, SARS SARS to murders, and for common cold variants,
[00:04:04.930]HEK 2 93 T cells were transfected with plasmas in encoding,
[00:04:08.710]either spike or nuclear capsid proteins before being fixed and seated onto
[00:04:12.700]slides. Then three antibodies were added to each well.
[00:04:16.180]The tertiary antibody has a fluorescent tag,
[00:04:18.730]so that when it stained with Evans blue dye,
[00:04:21.520]it causes all the cells in this well to fluoresce red under the microscope and
[00:04:25.450]causes cells with a positive antibody response to fluoresce green,
[00:04:29.340]slightly out as shown here. Each sample has three Wells, a mock,
[00:04:34.180]which is a negative control, the spike well, and the nucleocapsid well, okay.
[00:04:40.740]Prevalence of serological cross-reactivity against SARS.
[00:04:43.730]Cov two is shown here overall Tanzania and Sandy and samples showed
[00:04:48.380]significantly higher prevalence than us samples at a difference about 15%,
[00:04:53.150]a similar difference was found for the nuclear capsid protein.
[00:04:56.520]So that was pretty significant as well. However,
[00:04:59.030]the spike protein was not significantly different between the African and us
[00:05:02.600]samples showing a difference of only about two or 3%,
[00:05:06.860]now that it was evident that there's a significant difference in the serological
[00:05:10.400]cross-reactivity in Sub-Saharan African samples.
[00:05:13.580]We tested the samples against all other known human coronaviruses.
[00:05:17.540]As you can see on this slide, there's SARS MERS,
[00:05:20.240]and these four common cold variants. As you can see negative samples,
[00:05:24.620]only fluoresce red, while positive samples.
[00:05:26.870]Those with an antibody response have some green fluorescence around those cells
[00:05:31.670]after testing the samples against other human coronaviruses.
[00:05:35.060]We found that the prevalence of cross-reactivity against the spike protein was
[00:05:39.080]significant for all four common cold viruses,
[00:05:41.930]but was only significant against the nucleocapsid protein for the NL 63 and
[00:05:46.910]2 29 E common cold viruses.
[00:05:50.240]This indicates that SARS cov two likely shares the conserved spike region of
[00:05:54.080]common cold variants, but not of SARS or MERS sharing.
[00:05:57.920]This conserved region allows SARS Coby two to bind to the common cold antigens.
[00:06:02.030]Meaning prior exposure to exposure to these viruses may be a source of
[00:06:05.900]cross-reactive antibodies against SARS cov two, and might offer some protection.
[00:06:10.550]For the error.
[00:06:13.460]In conclusion,
[00:06:14.180]there appears to be a correlation between the low incidents of COVID infection
[00:06:17.840]and disease in Sub-Saharan Africa and the cross recognition of human
[00:06:21.920]coronaviruses and pre pandemic plasma samples.
[00:06:25.100]It was found that Subsaharan Africa samples had much higher cross recognition in
[00:06:29.120]comparison to us samples. Overall,
[00:06:31.880]this research suggests that prior exposure to other human Corona viruses may
[00:06:35.930]confer protection against COVID-19.
[00:06:39.200]Currently samples are being collected for the mid pantomime cohort.
[00:06:43.070]Right now we're performing IFA and real-time PCR on plasma,
[00:06:46.490]bugle and nasal pharyngeal samples, which were collected during the pandemic.
[00:06:50.270]And then we will be analyzing these samples using bearskin real time PCR,
[00:06:54.410]essentially tests for current infection with the virus and burst scan is a
[00:06:57.770]technology that essentially allows researchers to see all the different viruses
[00:07:01.460]that a person has been infected with. In.
[00:07:03.830]The last many years.
[00:07:06.320]The immunofluorescence assay used in this research tests for the presence of
[00:07:09.860]antibodies,
[00:07:10.850]but the presence of antibodies alone does not necessarily mean those.
[00:07:14.150]Antibodies will protect the host from disease for an antibody to elicit a
[00:07:18.200]protective immune response.
[00:07:19.580]It must be neutralizing to determine if the cross-reactive antibodies found are
[00:07:24.050]neutralizing and actually provide protection against COVID-19.
[00:07:27.560]We can perform neutralization assays.
[00:07:30.260]Next steps also include continuing the cancer study to determine the difference
[00:07:33.950]in cross-reactivity in cancer versus non-cancer patients. Ultimately,
[00:07:37.760]this research contributes to the understanding of cross-reactivity in relation
[00:07:41.360]to COVID-19 and other human Corona viruses,
[00:07:43.970]and may assist in the development of strategies to prevent infection and disease
[00:07:47.390]progression in patients with cancer.
[00:07:49.790]I would like to thank the UK program doctors would.
[00:07:52.310]And so the Nebraska center for neurology for providing me with the opportunity
[00:07:56.240]to assist in this research. Thank you.

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Prevalence of anti-SARS-CoV-2 Antibodies Among Cancer Patients and General Population in Dub-Saharan Africa

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